The Clinical And Experimental Studies Of IGFs Axis In Non-Small Cell Lung Cancer

Objective: To evaluate the clinical significance of the serum insulin-like growth factor 1 (IGF1),insulin-like growth factor2(IGF2) and insulin-like growth factor binding protein3(IGFBP3) in patients with non-small cell lung cancer(NSCLC) , explore biological effects activated by IGF1,IGF2,and the values of treatment targeting IGF1R-a strain by a specific monoclonal antibody in cell lines. Methods: The studies were conducted in clinic and larborary. All 143 patients with NSCLC were enrolled by the entry criteria.Serum IGF1,IGF2 and IGFBP3 were detected by ELISA . Serum levels of IGF1,IGF2,IGFBP3 among different stages, histological types, grades of differentiation,and between NSCLC vs. healthy controls,Xuzheng vs.Shizheng were compared by ANOVA analysis. Partial corelation analysis was processed on exploring the relativity of IGF1JGF2 and IGFBP3. The prognosis of more advanced NSCLC were evaluated by the regression analysis ,with inclusion of Kaplan-Meier and Cox proportional hazard regression model. In laboratory,SPC-A-1 cell line with highly expression of IGF1R was obtained by monoclonal techniques and distributed into B,C,D,E,F,G and H groups. Group B was setted as a control group. Group C,D,E,F,G and H were interfered with IGF1,IGF2,Ab3,IGFl+IGF2,IGFl+Ab3 and IGF2+Ab3 respectively. Cell proliferation and apoptosis were observed by MTT method,flow cytometry,quantities of Ki67 and electroscope at day 1,2,3,4,5 and 6 in the processes.The values between groups were analyzed by independent sample T test. Results:Serum levels of IGF1,IGF2 and IGFBP3 were not significant among different stages, histological types, grades of differentiation ,and between NSCLC vs. heathy controls, Xuzheng vs.Shizheng ,P>0.05.Howere,the significance of serum IGF1 and IGF2 was apparent between the local (I+II)and advaced (III+IV)diseases ( P=0.010, and 0.037) .Besides, serum IGF1, as an independent prognostic index for more advanced (IIb, IIIa, IIIb) NSCLC was found. In the laboratory, the indexes of cell proliferation and apoptosis were significantly different among groups. Conclusion: Serum IGF1, IGF2 ,which can be modified each other and take effects on IGFBP3, are an important indexes for evaluating the disease and prognosis of NSCLC.However, any of the three indexes shows little corelation with histological types,grades of differentiation,or Xuzheng vs. Shizheng and is not a valuable marker for the screening of NSCLC. The biological activities of IGF1,IGF2 studied in laboratory show their strong effects on improving the proliferation of SPC-A-1 cell line with high expression of IGF1R.The effects can be interrupted by Ab3,which is a special monoclonal antibody for the IGF1R-a strain.Besides,Ab3 can also improve the apoptosis of SPC-A-1 in vitro.